Human immunodeficiency virus (HIV) replication and T cell proliferation were investlgated in situ by a PCR-based analysis of individual microdissected splenic white pulps. Founder effects, revealed by an exqulslte compartmentalization of HIV genotypes and T cells, indicated the recruitment of latently infected CD4+ T cells through highly localized antigen presentation rather than the infection of CD4+ T lymphoblasts by blood-borne virus or immune complexes. HIV-infected white pulps could be infiltrated by HIV-specific cytotoxic T lymphocytes, thereby implicating them in CD4+ T cell destruction invlvo. Together these data describe an iterative and deleterious mechanism of antigendriven T cell recruitment and actlvatlon, as well as HIV replication and spread, with consequent destruction of the newly infected ceils.